Abstract
Advances in the understanding of neoplastic and non-neoplastic diseases of the thyroid, parathyroid glands, and adrenal glands continue to broaden our knowledge of these entities and the significance of the histologic and molecular findings to our patients. Although the histologic evaluation of the hematoxylin and eosin-stained tissue under the microscope remains the mainstay of diagnosis, the increasing understanding of the immunohistochemical and molecular features of these tumors brings insight into the pathogenesis of these lesions. The association with syndromes such as multiple endocrine neoplasia, Carney complex, and hyperparathyroidism jaw-tumor syndrome is a particularly intriguing feature of some endocrine tumors. This is a complex and fascinating area of pathology, but some diagnoses such as follicular variant of papillary thyroid carcinoma, atypical parathyroid adenomas, and adrenal cortical carcinomas remain very challenging. This chapter includes non-neoplastic and neoplastic diseases of the thyroid gland, parathyroid glands, and adrenal glands.
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Thyroid
DeLellis RA, Lloyd RV, Heitz PU, Eng C. Pathology and genetics of tumours of endocrine organs. In World Health Organization Classification of Tumours. Lyon, IARC Press, 2004, pp 320.
Rosai J, Carcangiu ML, DeLellis RA. Tumors of the thyroid gland. In Atlas of Tumor Pathology. Vol 5, 3rd Series edition. Washington, DC, Armed Forces Institute of Pathology, 1992, pp 343.
De Groot LJ, Quintans J. Causes of autoimmune thyroid disease. Endocr Rev. 1989;10:537–562.
Katz SM, Vickery AL. Fibrous variant of Hashimoto thyroiditis. Hum Pathol. 1974;5:161–170.
Volpé R. Pathogenesis of Graves disease: an overview. Clin Endocrinol Metab. 1978;7:3–29.
Erickson LA, Yousef OM, Jin L, Lohse CM, Pankratz VS, Lloyd RV. P27(kip1) expression distinguishes papillary hyperplasia in Graves’ disease from papillary thyroid carcinoma. Mod Pathol. 2000;13(9):1014–1019.
Woolner LB, McConaher WM, Beahrs OH. Invasive fibrous thyroiditis. J Clin Endocrinol Metab. 1957;17:201–220.
Erickson LA, Lloyd RV. Practical markers used in the diagnosis of endocrine tumors. Adv Anat Pathol. 2004;11(4):175–189.
Chen KT, Rosai J. Follicular variant of thyroid papillary carcinoma: clinicopathologic study of six cases. Am J Surg Pathol. 1977;1:123–130.
Lloyd RV, Erickson LA, Casey MB, et al. Observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma. Am J Surg Pathol. 2004; 28(10):1336–1340.
Erickson LA, Jin L, Wollan PC, Thompson GB, van Heerden J, Lloyd RV. Expression of p27(Kip1) and Ki-67 in benign and malignant thyroid tumors. Mod Pathol. 1998;11(2):169–174.
Carcangiu ML, Bianchi S. Diffuse sclerosing variant of papillary thyroid carcinoma: clinicopathologic study of 15 cases. Am J Surg Pathol. 1989;13:1041–1049.
Johnson TL, Lloyd RV, Thompson NW, Beierwaltes WH, Sisson JC. Prognostic implications of the tall cell variant of papillary thyroid carcinoma. Am J Surg Pathol. 1988;12:22–27.
Ferreiro JA, Hay ID, Lloyd RV. Columnar cell carcinoma of the thyroid: report of three additional cases. Hum Pathol. 1996;27:1156–1160
Baloch ZW, LiVolsi VA. Microcarcinoma of the thyroid. Adv Anat Pathol. 2006;13:69–75.
Lo CY, Chan WF, Lang BH, Lam KY, Wan KY. Papillary microcarcinoma: is there any difference between clinically overt and occult tumors? World J Surg. 2006;30:759–766.
Lupoli G, Vitale G, Caraglia M, Fittipaldi MR, Abbruzzese A, Tagliaferri P, Bianco AR. Familial papillary thyroid microcarcinoma: a new clinical entity. Lancet. 1999;353:637–639.
Evans HL. Columnar-cell carcinoma of the thyroid. A report of two cases of an aggressive variant of thyroid carcinoma. Am J Clin Pathol. 1986;85:77–80.
Nikiforov YE, Erickson LA, Nikiforova MN, Caudill CM, Lloyd RV. Solid variant of papillary thyroid carcinoma – incidence, clinical-pathologic characteristics, molecular analysis, and biologic behavior. Am J Surg Pathol. 2001; 25(12):1478–1484.
Herrera MF, Hay ID, Wu PS, et al. Hurthle cell (oxyphilic) papillary thyroid carcinoma: a variant with more aggressive biologic behavior. World J Surg. 1992;16:669–174; discussion 774–775.
Apel RL, Asa SL, LiVolsi VA. Papillary Hurthle cell carcinoma with lymphocytic stroma. “Warthin-like tumor” of the thyroid. Am J Surg Pathol. 1995;19:810–814.
Harach HR, Williams GT, Williams ED. Familial adenomatous polyposis associated thyroid carcinoma: a distinct type of follicular cell neoplasm. Histopathology. 1994;25:549–561.
Prasad ML, Pellegata NS, Huang Y, Nagaraja HN, de la Chapelle A, Kloos RT. Galectin-3, fibronectin-1, CITED-1, HBME1 and cytokeratin-19 immunohistochemistry is useful for the differential diagnosis of thyroid tumors. Mod Pathol. 2005;18:48–57.
Erickson LA, Lloyd RV. Utility of immunohistochemical markers in the diagnosis of follicular variant of papillary thyroid carcinoma. Adv Anat Pathol. 2008; 15(1):59–60.
Barroeta JE, Baloch ZW, Lal P, Pasha TL, Zhang PJ, LiVolsi VA. Diagnostic value of differential expression of CK19, Galectin-3, HBME-1, ERK, RET, and p16 in benign and malignant follicular-derived lesions of the thyroid: an immunohistochemical tissue microarray analysis. Endocr Pathol. 2006;17:225–234.
Nakamura N, Erickson LA, Jin L, Kajita S, Zhang H, Qian X, Rumilla K, Lloyd RV. Immunohistochemical separation of follicular variant of papillary thyroid carcinoma from follicular adenoma. Endocr Pathol. 2006;17:213–223.
Huang Y, Prasad M, Lemon WJ, et al. Gene expression in papillary thyroid carcinoma reveals highly consistent profiles. Proc Natl Acad Sci U S A. 2001;98:15044–15049.
Nakamura N, Carney JA, Jin L, Kajita S, Pallares J, Zhang H, Qian X, Sebo TJ, Erickson LA, Lloyd RV. RASSF1A and NORE1A methylation and BRAFV600E mutations in thyroid tumors. Lab Invest. 2005;85:1065–1075.
Cohen Y, Xing M, Mambo E, Guo Z, Wu G, Trink B, Beller U, Westra WH, Ladenson PW, Sidransky D. BRAF mutation in papillary thyroid carcinoma. J Natl Cancer Inst. 2003; 95:625–627.
Soares P, Trovisco V, Rocha AS, et al. BRAF mutations and RET/PTC rearrangements are alternative events in the etiopathogenesis of PTC. Oncogene. 2003;22:4578–4580.
Trovisco V, Vieira de Castro I, et al. BRAF mutations are associated with some histological types of papillary thyroid carcinoma. J Pathol. 2004;202:247–251.
Adeniran AJ, Zhu Z, Gandhi M, Steward DL, Fidler JP, Giordano TJ, Biddinger PW, Nikiforov YE. Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas. Am J Surg Pathol. 2006;30:216–222.
Lupi C, Giannini R, Ugolini C, et al. Association of BRAF V600E mutation with poor clinicopathological outcomes in 500 consecutive cases of papillary thyroid carcinoma. J Clin Endocrinol Metab. 2007;92:4085–4090.
Carney JA, Ryan J, Goellner JR. Hyalinizing trabecular adenoma of thyroid gland. Am J Surg Pathol. 1987;11:583–591.
Brennan MD, Bergstralh EJ, van Heerden JA, et al. Follicular thyroid cancer treated at Mayo Clinic, 1946 through 1970: initial manifestations, pathologic findings, therapy, and outcome. Mayo Clin Proc. 1991;66:11–22.
Van Heerden JA, Hay ID, Goellner JR, et al. Follicular thryroid carcinoma with capsular invasion alone non-threatening malignancy. Surgery. 1992;112:1130–1136.
Carcangiu ML, Bianchi S, Savino D, et al. Follicular Hürthle cell tumors of thyroid gland. Cancer. 1991;68:1944–1953.
Erickson LA, Jin L, Goellner JR, Lohse C, Pankratz VS, Zukerberg LR, Thompson GB, van Heerden JA, Grant CS, Lloyd RV. Pathologic features, proliferative activity, and cyclin D1 expression in Hurthle cell neoplasms of the thyroid. Mod Pathol. 2000;13(2):186–192.
Erickson LA, Jalal SM, Goellner JR, Law ME, Harwood A, Jin L, Roche PC, Lloyd RV. Analysis of Hurthle cell neoplasms of the thyroid by interphase fluorescence in situ hybridization. Am J Surg Pathol. 2001; 25(7):911–917.
Carcangiu ML, Zampi G, Rosai J. Poorly differentiated (“insular”) thyroid carcinoma reinterpretation of Langhans’ “wuchernde Struma.” Am J Surg Pathol. 1984;8:655–668.
Carcanjiu ML, Steeper T, Zampi G, et al. Anaplastic thyroid carcinoma study of 70 cases. Am J Clin Pathol. 1985;83:135–158.
Perry A, Molberg K, Albores-Saavedra J. Physiologic versus neoplastic C-cell hyperplasia of the thyroid: separation of distinct histologic and biologic entities. Cancer. 1996;77:750–756.
Ogilvie JB, Kebebew E. Indication and timing of thyroid surgery for patients with hereditary medullary thyroid cancer syndromes. J Natl Compr Canc Netw. 2006;4:139–147.
Brandi ML, Gagel RF, Angeli A, et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab. 2001;86:5658–5671.
Oliveira AM, Tazelaar HD, Myers JL, Erickson LA, Lloyd RV. Thyroid transcription factor-1 distinguishes metastatic pulmonary from well-differentiated neuroendocrine tumors of other sites. Am J Surg Pathol. 2001;25(6):815–819.
Donis-Keller H, Dou S, Chi D, et al. Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC. Hum Mol Genet. 1993;2:851–856.
Parathryoid
Bondeson L, Grimelius L, DeLellis RA, Lloyd R, Akerstrom G, Larsson C, Arnold A, Eng C, Shane E, Bilezekian JP. Parathyroid carcinoma. In Pathology and Genetics of Tumours of Endocrine Organs. Edited by RA DeLellis, Lloyd, R.V., Heitz. P.U., Eng, C. Lyon, IARC Press, 2004, pp 124–132
Marx SJ. Hyperparathyroid and hypoparathyroid disorders. N Engl J Med. 2000;343:1863–1875.
Erickson LA, Lloyd RV. Familial disorders of the pathology of the parathyroid gland. Diagn Histopathol. 2009.
Castleman B, Schwantz A, Roth SI. Parathyroid hyperplasia in primary hyperparathyroidism: review of 85 cases. Cancer. 1976;38:1668–1675.
Black WC III, Haff RC. Surgical pathology of parathyroid chief cell hyperplasia. Am J Clin Pathol. 1970;53:565–579.
Chandur-Mnaymneh L, Kimura N. Parathyroid adenoma histopathologic definition with study of 172 cases of primary hyperparathyroidism. Am J Pathol. 1984;115:70–83.
Chow LS, Erickson LA, Abu-Lebdeh HS, Wermers RA. Parathyroid lipoadenomas: a rare cause of primary hyperparathyroidism. Endocr Pract. 2006;12(2):131–136.
Erickson LA, Jin L, Papotti M, Lloyd RV. Oxyphil parathyroid carcinomas: a clinicopathologic and immunohistochemical study of 10 cases. Am J Surg Pathol. 2002;26:344–399.
Erickson LA, Jin L, Wollan P, et al. Parathyroid hyperplasia, adenomas, and carcinomas differential expression of p27(Kip1) protein. Am J Surg Pathol. 1999;23(3):288–295
Marx SJ, Agarwal SK, Kester MB, et al. Multiple endocrine neoplasia type 1: clinical and genetic features of the hereditary endocrine neoplasias. Recent Prog Horm Res. 1999;54:397–438; discussion 438–439.
Lemos MC, Thakker RV. Multiple endocrine neoplasia type 1 (MEN1): analysis of 1336 mutations reported in the first decade following identification of the gene. Hum Mutat. 2008;29:22–32.
Haven CJ, van Puijenbroek M, Tan MH, et al. Identification of MEN1 and HRPT2 somatic mutations in paraffin-embedded (sporadic) parathyroid carcinomas. Clin Endocrinol (Oxf). 2007;67:370–376.
Erickson LA, Jin L, Wollan P, Thompson GB, van Heerden JA, Lloyd RV. Parathyroid hyperplasia, adenomas, and carcinomas: differential expression of p27Kip1 protein. Am J Surg Pathol. 1999;23:288–295.
Erickson LA, Jalal SM, Harwood A, Shearer B, Jin L, Lloyd RV. Analysis of parathyroid neoplasms by interphase fluorescence in situ hybridization. Am J Surg Pathol. 2004;28:578–584.
Hsi ED, Zukerberg LR, Yang WI, Arnold A. Cyclin D1/PRAD1 expression in parathyroid adenomas: an immunohistochemical study. J Clin Endocrinol Metab. 1996;81:1736–1739.
Oishi S, Sato T, Takiguchi-Shirahama S, Nakamura Y. Mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A (Sipple’s syndrome). Endocr J. 1995;42:527–536.
Janicic N, Soliman E, Pausova Z, et al. Mapping of the calcium-sensing receptor gene (CASR) to human chromosome 3q13.3-21 by fluorescence in situ hybridization, and localization to rat chromosome 11 and mouse chromosome 16. Mamm Genome. 1995;6:798–801.
Hosokawa Y, Pollak MR, Brown EM, Arnold A. Mutational analysis of the extracellular Ca(2+)-sensing receptor gene in human parathyroid tumors. J Clin Endocrinol Metab. 1995;80:3107–3110.
Cetani F, Pardi E, Borsari S, et al. Genetic analyses of the HRPT2 gene in primary hyperparathyroidism: germline and somatic mutations in familial and sporadic parathyroid tumors. J Clin Endocrinol Metab. 2004;89:5583–5591.
Carpten JD, Robbins CM, Villablanca A, et al. HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome. Nat Genet. 2002;32:676–680.
Szabo J, Heath B, Hill VM, Jackson CE, Zarbo RJ, Mallette LE, Chew SL, Besser GM, Thakker RV, Huff V, et al. Hereditary hyperparathyroidism-jaw tumor syndrome: the endocrine tumor gene HRPT2 maps to chromosome 1q21-q31. Am J Hum Genet. 1995;56:944–950.
Shattuck TM, Valimaki S, Obara T, et al. Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. N Engl J Med. 2003;349:1722–1729.
Juhlin C, Larsson C, Yakoleva T, et al. Loss of parafibromin expression in a subset of parathyroid adenomas. Endocr Relat Cancer 2006;13:509–523.
Adrenal
Sasano H, Suzuki T, Moriya T. Adrenal cortex. In Endocrine Pathology: Differential Diagnosis and Molecular Advances. Edited by RV Lloyd. Totowa, NJ, Humana Press, 2004, pp 211–226
Lack EE. Pathology of Adrenal and Extra-Adrenal Paraganglia. Philadelphia, PA, WB Saunders Co, 1994.
Shenoy BV, Carpenter PC, Carney JA. Bilateral primary pigmented nodular adrenocortical disease: rare cause of Cushing syndrome. Am J Surg Pathol. 1984;8:335–344.
Carney JA, Sizemore GW, Sheps SG. Adrenal medullary disease in multiple endocrine neoplasia, type 2: pheochromocytoma and its precursors. Am J Clin Pathol. 1976;66:279–290.
Erickson LA, Lloyd RV, Hartman R, Thompson G. Cystic adrenal neoplasms. Cancer. 2004;101(7):1537–1544.
Hough AJ, Hollifield HW, Page DL, et al. Prognostic factors in adrenal cortical tumors. Am J Clin Pathol. 1979;72:390–399.
Kendrick ML, Lloyd R, Erickson L, Farley DR, Grant CS, Thompson GB, Rowland C, Young WF Jr, van Heerden JA. Adrenocortical carcinoma: surgical progress or status quo? Arch Surg. 2001;136(5):543–549.
Lack EE, Mulvihill JJ, Travis WD, et al. Adrenal cortical neoplasms in pediatric and adolescent age group: clinicopathologic study of 30 cases with emphasis on epidemiological and prognostic factors. Pathol Annu. 1992;27:1–53.
Macadam RF. Black adenoma of human adrenal cortex. Cancer. 1971;27:116–119.
Bodie B, Novick AC, Pontes JE, Straffon RA, Montie JE, Babiak T, Sheeler L, Schumacher P. The Cleveland Clinic experience with adrenal cortical carcinoma. J Urol. 1989;141:257–260.
Crucitti F, Bellantone R, Ferrante A, Boscherini M, Crucitti P. The Italian Registry for Adrenal Cortical Carcinoma: analysis of a multiinstitutional series of 129 patients. The ACC Italian Registry Study Group. Surgery. 1996;119:161–170.
Erickson LA, Jin L, Sebo TJ, Lohse C, Pankratz VS, Kendrick ML, van Heerden JA, Thompson GB, Grant CS, Lloyd RV. Pathologic features and expression of insulin-like growth factor-2 in adrenocortical neoplasms. Endocr Pathol. 2001;12:429–435.
van Slooten H, Schaberg A, Smeenk D, Moolenaar AJ. Morphologic characteristics of benign and malignant adrenocortical tumors. Cancer. 1985;55:766–773.
Weiss LM. Comparative histologic study of 43 metastasizing and nonmetastasizing adrenocortical tumors. Am J Surg Pathol. 1984;8:163–169.
Weiss LM, Medeiros LJ, Vickery AL, Jr. Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol. 1989;13:202–206.
Wieneke JA, Thompson LD, Heffess CS. Adrenal cortical neoplasms in the pediatric population: a clinicopathologic and immunophenotypic analysis of 83 patients. Am J Surg Pathol. 2003;27:867–881.
Brown FM, Gaffey TA, Wold LE, Lloyd RV. Myxoid neoplasms of the adrenal cortex: a rare histologic variant. Am J Surg Pathol. 2000;24:396–401.
Loy TS, Phillips RW, Linder CL. A103 immunostaining in the diagnosis of adrenal cortical tumors: an immunohistochemical study of 316 cases. Arch Pathol Lab Med. 2002;126:170–172.
Lloyd RV, Blaivas M, Wilson BS. Distribution of chromogranin and S-100 protein in normal and abnormal adrenal medullary tissues. Arch Pathol Lab Med. 1985;109:633–635.
Lloyd RV, Shapiro B, Sisson JC, et al. An immunohistochemical study of pheochromocytomas. Arch Pathol Lab Med. 1984;108:541–544.
Medeiros LJ, Wolf BC, Balogh K, et al. Adrenal pheochromocytoma: clinicopathologic review of 60 cases. Hum Pathol. 1985;16:580–589.
Beckwith JB, Martin RF. Observations on histopathology of neuroblastoma. J Pediatr Surg. 1968;3:106–110.
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Erickson, L.A. (2011). Endocrine Pathology. In: Cheng, L., Bostwick, D. (eds) Essentials of Anatomic Pathology. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6043-6_20
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